Nature has the ingenious capability to design spiky topological features at the macro-and nanoscales, which exhibits fascinating interface adhesive properties by means of multivalent interactions. Following a biomimetic approach, such as nanoscale virus particles are highly infectious toward host cells, a range of organic and inorganic spiky particles (virus-like nanostructures) have been precisely engineered for diverse biomedical applications. Generally, organic virus-like particles (VLPs) derived from viral capsids (often termed as virosomes) have been extensively studied and reviewed, but concomitant concerns regarding immunogenicity and risks of mutagenesis limit clinical potential of organic VLPs. In contrast, inorganic VLPs (viral-mimicking topography) possess fascinating physicochemical characteristics, such as excellent electrical, optical, magnetic, mechanical and catalytic properties, which make them particularly suitable for biomedical applications. Alternatively, there is no comprehensive review related to inorganic VLPs engineered with non-viral shell for biomedical applications. Hence, in this review, we present a brief overview on inorganic VLPs, followed by summarizing the construction and properties of virus-like nanostructures, as well as the mechanisms of nano-bio interface interactions initiated by spiky topography. Furthermore, we focus on the recent advances of VLPs for biomedical applications (including biosensing, antibacterial therapy and cancer treatment). Finally, the future outlook and emerging challenges will be presented. This review aims to provide future scope of the rational design of inorganic non-viral vectors, especially with respect to gene-based therapy platforms.